FDA Update on Oversight of Prescription Drug Promotion

Thomas AbramsDirector

Office of Prescription Drug PromotionFood and Drug Administration

November 6, 2019

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Qsymia Untitled Letter

• Consumer website

• Indication:

– Qsymia is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (BMI) of:

• 30 kg/m2 or greater (obese) or

• 27 kg/m2 or greater (overweight) in the presence of at least one weight related comorbidity such as hypertension, type 2 diabetes mellitus, or dyslipidemia.

– Limitations of Use

• The effect of Qsymia on cardiovascular morbidity and mortality has not been established.

• The safety and effectiveness of Qsymia in combination with other products intended for weight loss, including prescription and over-the-counter drugs, and herbal preparations, have not been established.

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Risk Information for Qsymia• Contraindications include:

– Pregnancy

– Glaucoma

– Hyperthyroidism

– During or within 14 days following the administration of monoamine oxidase inhibitors

• Warnings and precautions include:– Fetal toxicity

– Increase in heart rate

– Suicidal behavior and ideation

– Acute myopia and secondary angle closure glaucoma

– Mood and sleep disorders

– Cognitive impairment

– Metabolic acidosis

– Elevated creatinine

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False or Misleading Claimsabout Efficacy

• Claims that Qsymia can help patients lose weight 3x faster than diet and exercise alone are misleading.

– The sponsor cited calculated ratios of the amount of weight loss at specific points in time from the clinical studies.

– These calculations do not support claims regarding the rate of weight loss.

– In addition, the clinical studies were designed to evaluate the amount of weight loss and cannot be used to support claims regarding rate of weight loss.

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False or Misleading Claimsabout Efficacy

• The webpage– Omits material information from the full indication about the

relative effect of diet and exercise, as well as contextual information about weight loss results in the placebo group, and thereby suggests that the results can be attributable to Qsymia alone

– Selectively presents the more favorable absolute amount of weight loss and reduction in waist circumference, which fails to account for an individual’s baseline weight and waist circumference

– Selectively presents the results for patients who remained on Qsymia at distinct points in time and fails to account for the substantial number of patients who withdrew from the trial

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False or Misleading RiskPresentation

• The webpage

– Fails to present information relating to contraindications, warnings, precautions, and adverse reactions for Qsymia with a prominence and readability reasonably comparable to the presentation of information relating to benefits for Qsymia

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ParaGard Untitled Letter

• Direct-to-consumer television advertisement (TV ad)

• Indication:

– ParaGard is indicated for intrauterine contraception for up to 10 years.

• Contraindications include:– Pregnancy or suspicion of pregnancy

– Abnormalities of the uterus resulting in distortion of the uterine cavity

– Acute pelvic inflammatory disease, or current behavior suggesting a high risk for pelvic inflammatory disease

– Postpartum endometritis or postabortal endometritis in the past 3 months

– Known or suspected uterine or cervical malignancy

– Genital bleeding of unknown etiology

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Warnings and Precautionsfor ParaGard

• Warnings include:– Intrauterine pregnancy

– Ectopic pregnancy

– Pelvic infection

– Immunocompromise

– Embedment

– Perforation

– Expulsion

– Wilson’s Disease (a rare genetic disease affecting copper excretion)

• Precautions include:– Vaginal bleeding

– Vasovagal reactions, including fainting

– Expulsion following placement after a birth or abortion

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ParaGard TV Ad

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False or Misleading RiskPresentation

• The TV ad:

– Presents claims and/or representations about the uses and benefits of ParaGard

– Fails to include important risk information associated with ParaGard

– Misleadingly suggests that ParaGard is safer than has been demonstrated

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False or Misleading RiskPresentation

• The TV ad also includes the following claims and presentations (emphasis original):

– “No hormones! I found a birth control with no hormones! ParaGard’s 100% hormone-free…!”

– “No hormones not an ounce! With an ingredient I can pronounce.”

– “100% HORMONE FREE”

– “1 SIMPLE ACTIVE INGREDIENT”

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Stendra Warning Letter• Direct-to-consumer print advertisement (ad) and banners

• Indication:

– Stendra is a phosphodiesterase 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED).

• Contraindications:– Using any form of organic nitrate or a guanylate cyclase stimulator

– Known hypersensitivity to any component of the tablet

• Warnings and precautions include:– Cardiovascular risks

– Concomitant use of CYP3A4 inhibitors, alpha-blockers and other antihypertensives, alcohol, and other PDE5 inhibitors or ED therapies

– Prolonged erection

– Sudden vision or hearing loss

– Effects on bleeding

– Counseling patients about sexually transmitted diseases

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Lack of Adequate Directionsfor Use

• The headline claim “Treat ED and Reduce Risk of Heart Failure with a PDE-5 Inhibitor”

– Provides evidence that Stendra is intended for a new use for which it lacks approval, and for which its labeling does not provide adequate directions for use

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False or MisleadingRisk Presentation

• The print ad

– Omits serious risks associated with Stendra and fails to provide material information about the consequences that may result from its use

– Fails to present information about risks with a prominence and readability reasonably comparable with the presentation of information related to the effectiveness, thus minimizing the risks associated with Stendra

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False or MisleadingRisk Presentation

• The print ad includes the following claims (underlined emphasis added)

– “Treat ED and Reduce Risk of Heart Failure with a PDE-5 Inhibitor”

– “Stendra (Avanafil) is … safe and effective for those with heart disease ….”

– “Stendra is the next-generation PDE-5 inhibitor that improves erectile dysfunction.”

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False or MisleadingRisk Presentation

• The print ad

– Omits important serious risk information for Stendra

– Fails to present information about the risks with a prominence and readability reasonably comparable with the presentation of information related to the effectiveness

– Implies that Stendra is safe for all patients with heart disease

– Suggests that Stendra is safer or more effective than its competitors

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False or MisleadingRisk Presentation

• The banners include the following statements but fail to communicate any risk information about Stendra:

– “Get Hard & Stay Hard”

– “Indulge in life’s sweetest pleasures whenever you want”

– “Ask your doctor for more information”

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False or Misleading Claimsabout Efficacy

• The banners also fail to communicate material information regarding the indication for Stendra (underlined emphasis added):

– Stendra is a PDE5 inhibitor indicated for the treatment of erectile dysfunction.

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False or MisleadingRisk Presentation

• The banners include the following statements but fail to include any of the contraindications or warnings:

– “The ED Pill For Your Lifestyle”

– “Stendra prescriptions can be taken with or without food and alcohol”

– “The Fast-Acting ED Prescription”

– “Common side effects include: headache, flushing, and nasal congestion”

– “Ask your doctor for more information”

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OPDP Web Resources

• OPDP Home Page– http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CD

ER/ucm090142.htm

• Guidances – http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CD

ER/ucm109905.htm#Guidances

• Social Science Research– https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CD

ER/ucm090276.htm

• Warning and Untitled Letters– www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesb

yFDA/WarningLettersandNoticeofViolationLetterstoPharmaceuticalCompanies/default.htm

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OPDP Contact Information

• Telephone Number

– 301-796-1200

• Fax Numbers

– 301-847-8444

– 301-847-8445

• Submission Address

– Food and Drug AdministrationCenter for Drug Evaluation and ResearchOffice of Prescription Drug Promotion5901-B Ammendale RoadBeltsville, MD 20705-1266